184704. lajstromszámú szabadalom • Eljárás biológiailag aktív enkefalin analógok előállítására

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184.704

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Me-MeTyr.D- Ala.Gly .Phe .Leu.OH acetá t Me-MeTyr.Gly.Gly.Tyr.Leu.oh acetát Me-MeTyr.Gly. Ala .Phe.Leu.OH HCl Me-MeTyr.Gly.Gly.Phe.Leu.OH HCl Me-MeTyr.D-Ala.Gly.Phe.Leu.OMe HCl Me-MeTyr.Gly.Gly.Phe.Leu.OMe HCl Me-MeTyr.D.Ala.Gly.Phe.D-Leu.OH HCl Me-MeTyr.D-Ala.Gly.Phe.D-Leu.OMe HCl Me-D-MeTyr.Gly.Gly.Phe.Leu.OH HCl , ,

Me-MeTyr.D-MeAla.Gly.Phe.D-Leu.OHHCl 0.332,0,763,0.814 H.Tyr.Gly.Gly.Phe.Leu.Tyr.Gly.OH HCl 0.863,0.844 H.Tyr.D-Ala.Gly.His.Leu.OH 2HC1 0.262, Ö,473. 0.524

H.Tyr.D-Ala.Gly.Phe.D-Leu.Phe.Gly.OH HCl 0,632

H.Tyr.Gly.Gly.Phe.Met(0).OH HCl 0.182,0,563,0,514

H.Tyr.D-Ala.Gly.Phe.D-Leu.Lys.Lys.OH 0.443,0,384 discutât

H.Tyr.D-Trp.Gly.Phe.Leu.OH nátrium só 0.762,0,843 Ac

0.542,0.623, 0.664 0.352, Ö.633,0.874 0.552,0.663,0.804 0.452, Ö.653,0.584 0.452, Ö.973,0.974 0.382,0.923,0.964 0.402,0,863,0.784 0.412, Ö.753, 0.964 0.362,0.893,0.604

0.722,

0.762

H.Tyr.D-Ala.Gly .Phe.D-Leu.Tyr.OH H.Tyr.D-Trp.Gly.Phe.D-Leu.OH HCl H.Tyr.D-Ala.Gly.Phe(4Cl).D-Leu.OH HO 0,42“ A Me

H.Tyr.Gly.Gly.Tyr.Leu.OH HC!

H.Tyr.D-Ala.Gly ,Phe(4Cl).D-Leu.OMe HCl

0.67s

0.552,0.933 0.655

, 0.19*

0.52s 0.562

0.623,0.64s 0.552,0.51s 0.622,0.75\0.924 0.522,0.533A 0.482,0.583A 0.432,0.483 0.813,0.844,0.68s

H.Tyr.Gly.Gly.Phe.D-Leu.OMe HCl H.MeTyr.D-Ala.Gly.Phe.D-Leu.NH2 HCl II.Tyr.Gly.Gly.Phe.D-Met.OMe HCl H.Tyr.Gly.Gly.Phe.D-Met.OH HCl H.MeTyr.D-Ala.Gly.Phe.D-Met.OMe HCl H.Tyr. Asn.Gly.Phe.D-Leu.OH H.Tyr. Asn.Gly.Phe.D-Leu.OH Me-MeTyr.MeAla.Glÿ.Phe.D-Leu.OH HCl H.Tyr.Gly.Gly.Phe.O-acetilleucinol HCl -O-acetilleucinol = -NH.CH(CH2 ,CH(CH3)2 ).

,CH2O.CO.CH3

H.Tyr.Gly.Gly.Phe.leucinol HCl 0.813,0.754,0.68*-leucinol = -NH.CH(CH2 ,CH(CH3)2 ).CH2 .OH H.Tyr.Ala(aMe)Gly.Phe.D-Leu.OH HCl -Ala(aMe> = -NH.C(CH3)2 .COH.Tyr.Ala(aMe).Gly.Phe.D-Leu.OMe HCl Hj3HomoTyr.Gly.Gly.Phe.Leu.OH HCl H.Tyr.D-Ala.Gly .Phe.D-|3HomoLeu.OHH( H.Tyr.D-Ala.Gly.Phe.Leu-tetrazol HCl H.Tyr.D-Ala.Gly.Phe.D-Leu-tetrazol HCl

♦39,2°

+31,3°

♦38,2°

+52,4°

+62,4°

+66,4°-67,4°

+58,4°-4,79°

+20,8°

+13,4°

+18,7°

(c=0,4)

(c=0,4)

(c=l,0)

(c=l,0)

(c=o,n (c*i,o) (c=0,5) (c=Q,2) (c=o,r (c=l (c=0,5) (C--0.2)

Ï]

♦12,0° (c=0,5) -4,72° (c=l,0)

+35,6° (c=0,5)

+16,58° (c=2)á -4,56° (c=0,2)

+28,4°

+36,5°

+40,0°

+50,7°

+43,7°

+38,3°

+59,4°-11,8°-21,0°

+13,8°

0.552,0.773,0.594

+25,4°

0.702,0.893,0.954

+ 28,5'

0.532,0.633,0.524

1

£

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1 0.58\0.823,0.494

+10,7°

0.602,0.923,0.964

+48,2°

0.602,0.903,0.944

+39,7° (

(c=0,l)

(c=0,5)

(o0,5)

(c=l)

(c=0,5)

(o=0,5)

(c=0f12)

(c=0,52)

(c=0,5)

(c-0,1)

(c=0,52)

' (c=0,5) (c=0,5) (c=0,5) (c=0,l)

CH(CH3)2

£h2

•Leu-tetrazol = -NH-dlH-C-NH

I' \ N N

Y

115.

116.

119.

120. 121. 122. 123.

124.

H.DOPA.D-Ala.Gly.Phe.D-Leu.OH HCl H.D-DOPA.D-Ala.Gly.Phe.D-Leu.OH HG H.MeTyr.D-Ala.Gly.Phe.D-Met.NHEt HCl H.MeTyr.D-Ala.Gly.Phe.D-Met.OH HCl H.MeTyr.D-Aia.Giy.Phe.D-Met.NH2 HCl H.Phe(4Cl).D-Ala.Gly.Phe.D-Leu.OH acetát H.Tyr.D-Ala.Gly.Phe(4Cl).D-Leu.NHEt HCl ^le

0.562,0.723 0.582,0.683 0.592,0.843,0.904 0.52J,0.713,0.694 0.522,0.723,0.854 0.653 A, 0.454A 0.632,0.683A, 0.68s

H.Tyr.Gly.Gly.Tyr. Leu.OMe HCl

0.622,0.963,0.15*

+29,9° (c=0,l)

+9,8° (c=0,l)

+59,7° (c=l)

+34,7° (c=l)

+48,9° (c=l)-0,78° (c=0,2)

+40,7° (c=0,5)

+18,9° (c=l)

= kloroform:metanol:321 ecetsav (120:90:5) 4A = kloroform:metanol:880 ammónia (120:90:5)